SU628822A3 - Method of producing 4'-epy-6'-oxyadriamycin hydrochloride - Google Patents

Method of producing 4'-epy-6'-oxyadriamycin hydrochloride

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Publication number
SU628822A3
SU628822A3 SU762387269A SU2387269A SU628822A3 SU 628822 A3 SU628822 A3 SU 628822A3 SU 762387269 A SU762387269 A SU 762387269A SU 2387269 A SU2387269 A SU 2387269A SU 628822 A3 SU628822 A3 SU 628822A3
Authority
SU
USSR - Soviet Union
Prior art keywords
chloroform
solution
hydrochloride
epi
methanol
Prior art date
Application number
SU762387269A
Other languages
Russian (ru)
Inventor
Аркамоне Федерико
Барджиотти Альберто
Кассинелли Джузеппе
Ди Марко Аурелио
Original Assignee
Сочиета Фармасьютичи Италиа С.П.А (Фирма)
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
Application filed by Сочиета Фармасьютичи Италиа С.П.А (Фирма) filed Critical Сочиета Фармасьютичи Италиа С.П.А (Фирма)
Application granted granted Critical
Publication of SU628822A3 publication Critical patent/SU628822A3/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/20—Carbocyclic rings
    • C07H15/24—Condensed ring systems having three or more rings
    • C07H15/252—Naphthacene radicals, e.g. daunomycins, adriamycins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
    • C07D309/16—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D309/28—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D309/30—Oxygen atoms, e.g. delta-lactones
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Saccharide Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Description

1one

Изобретение относитс  к способу получени  нового соединени , а именно к способу получени  хлоргидрата 4 -эпи-б -оксиадриамицина, обладающего биологической активностью.The invention relates to a process for the preparation of a novel compound, namely to a process for the preparation of 4-epi-b-hydroxy-adriamycin hydrochloride, which has biological activity.

Цель изобретени  - получение нового соединени , обладающего ценными свойствами. Хлоргидрат 4-эпи-б оксиадриамицина получают взаимодействием 4-эпи-6-оксидауномицина в смеси метилового спирта и безводного диоксана с раствором брома в хлороформе . Полученный 14-бром- 4-эпи-6оксидауномицин обрабатывают 0,25 н. раствором бромистоводородной кислоты в ацетоне с последующим гидролизсм водным pacTBOpoNf формиата натри  и .затем обработкой раствором 1 н сол ной кислоты. Целевой продукт выдел ют известными приемами в виде хлоргидрата .The purpose of the invention is to obtain a new compound with valuable properties. 4-epi-b hydroxyadriamycin hydrochloride is obtained by reacting 4-epi-6-oxidunomycin in a mixture of methyl alcohol and anhydrous dioxane with a solution of bromine in chloroform. The resulting 14-bromo-4-epi-6oxedounomycin is treated with 0.25 n. a solution of hydrobromic acid in acetone, followed by hydrolysis with aqueous pacTBOpoNf sodium formate and then treatment with a solution of 1 n hydrochloric acid. The desired product is isolated by conventional techniques as a hydrochloride.

Получение 4-эпи-6 окПример , сиа дриамицина.Preparation of 4-epi-6 ok Example of sidriamycin.

0,25 г 4-эпи-6 -оксидауномицина раствор ют в смеси 3,5 метилового спирта и 10 мл безводного диокеана и при перемешивании обрабатывают 0,9 мл раствора 0,88 г брома в 10 мл хлороформа. Реакционную смесь спуст  1 ч после выдерживани  при комнатной температуре выливают при перемешивании в 75 мл диэтилового эфира. Неочищенный 14- РОм-4-эпи-6-оксидауномицин отфильтровывают и раствор ют в сме0 си 5 мл ацетона и 5 мл 0,25 н.раствора бромистоводородной кислоты. Спуст  12 ч после сто ни  при комнатной температуре кислый раствор экстрагируют сначала хлороформом дл  0.25 g of 4-epi-6-oksidaunomycin is dissolved in a mixture of 3.5 methyl alcohol and 10 ml of anhydrous diokene and with stirring, treated with 0.9 ml of a solution of 0.88 g of bromine in 10 ml of chloroform. The reaction mixture after 1 h after keeping at room temperature is poured with stirring into 75 ml of diethyl ether. Untreated 14-POM-4-epi-6-oxidunomycin is filtered off and dissolved in a mixture of 5 ml of acetone and 5 ml of 0.25 n hydrobromic acid solution. After 12 hours from standing at room temperature, the acidic solution is extracted first with chloroform for

5 удалени  агликонов, затем Н -бутанолом . Экстракции провод т несколько раз до тех пор, пока весь окрашенный продукт не перейдет в органический слой.5 removal of aglycone, then H-butanol. The extractions are carried out several times until the entire colored product passes into the organic layer.

ОABOUT

После концентрировани  экстрактов н-бутанола под вакуумом получают 0,27 г 14-бром-производного. Этот продукт раствор ют в 10 мл воды и обрабатывают 0,5 г формиата натри . Спуст  48 ч после сто ни  при комнатной температуре реакционную смесь упаривают досуха под вакуумох и остаток , растворенный в 30 мл смеси After concentrating the extracts of n-butanol under vacuum, 0.27 g of a 14-bromo derivative is obtained. This product is dissolved in 10 ml of water and treated with 0.5 g of sodium formate. 48 hours after standing at room temperature, the reaction mixture is evaporated to dryness under a vacuum and the residue dissolved in 30 ml of the mixture.

Claims (1)

о хлороформа и метанола(2:1 по объему). 6 промывают 10 мл 1%-ного водного раствора N аНСО. Водную фазу экстрагируют хлороформом многократно до тех пор, пока весь окрашенный продукт не перейдет в органический слой. Соединенные хлороформные экстракты сушат над безводным сульфатом натри ,концентрируют при пониженном давлении до малого объема и обрабатывают 1 эквивалентом 1 н. сол ной кис лоты в безводном метаноле. Добавлением 10 объемов диэтилового эфира получают 0,125 г 4-эпи-6-оксиадриами цина в виде хлоргидрата. Т,пл. 180 С с разложением,сс 1+216 (,01 СНдОН). Хроматографическа  величина равна 0,5 на Кизельгель НР -пластин как (по Мерку), используетс  смесь растворителей: хлороформ, метанол и вода (130:60:10 по объему). Формула изобретени  Способ получени  хлоргидрата 4эпи-б-оксиадриамицина ., отличающийс  тем, что 4-эпи-б-оксидауномицин в смеси метилового спирта и безводного диоксана подвергают взаимодействию с раствором брома в хлороформе , полученный 14-бром-4-эпи-6-оксидауномицин обрабатывают 0,25 н,раствором бромистоводородной кислоты в ацетоне с последующим гидролизом водным раствором формиата натри  и обработкой раствором 1 н.сол ной кислоты . Источники информации, прин тые во внимание при экспертизе: 1. Фьюзон Р. Реакции органических соединений, Москва, Rnp, 1966, с,531.o chloroform and methanol (2: 1 by volume). 6 washed with 10 ml of a 1% aqueous solution of N ANSO. The aqueous phase is extracted with chloroform several times until the entire colored product passes into the organic layer. The combined chloroform extracts are dried over anhydrous sodium sulfate, concentrated under reduced pressure to a small volume and treated with 1 equivalent of 1N. hydrochloric acid in anhydrous methanol. By adding 10 volumes of diethyl ether, 0.125 g of cin 4-epi-6-oxyadriam is obtained in the form of hydrochloride. T, pl. 180 C with decomposition, ss 1 + 216 (, 01 SNDN). The chromatographic value is 0.5 on Kieselgel HP -Plate as (according to Merck), a mixture of solvents is used: chloroform, methanol and water (130: 60: 10 by volume). DETAILED DESCRIPTION OF THE INVENTION A method for the preparation of 4epi-b-hydroxyadriamycin hydrochloride, characterized in that 4-epibd-oxi-dunomycin in a mixture of methyl alcohol and anhydrous dioxane is reacted with a bromine solution in chloroform, obtained 14-bromo-4-epi-6-oxydunomycin treated with 0.25 N, a solution of hydrobromic acid in acetone, followed by hydrolysis with an aqueous solution of sodium formate and treatment with a solution of 1N hydrochloric acid. Sources of information taken into account in the examination: 1. R. Fuson. Reactions of organic compounds, Moscow, Rnp, 1966, p. 531.
SU762387269A 1974-10-29 1976-08-10 Method of producing 4'-epy-6'-oxyadriamycin hydrochloride SU628822A3 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GB4664474A GB1470860A (en) 1974-10-29 1974-10-29 Anthracycline glycosides

Publications (1)

Publication Number Publication Date
SU628822A3 true SU628822A3 (en) 1978-10-15

Family

ID=10442049

Family Applications (2)

Application Number Title Priority Date Filing Date
SU752184006A SU646913A3 (en) 1974-10-29 1975-10-27 Method of produding 4,epi-6, oxydaunomicine hydrochloride
SU762387269A SU628822A3 (en) 1974-10-29 1976-08-10 Method of producing 4'-epy-6'-oxyadriamycin hydrochloride

Family Applications Before (1)

Application Number Title Priority Date Filing Date
SU752184006A SU646913A3 (en) 1974-10-29 1975-10-27 Method of produding 4,epi-6, oxydaunomicine hydrochloride

Country Status (17)

Country Link
US (1) US4025623A (en)
JP (2) JPS5951559B2 (en)
AT (1) AT340591B (en)
AU (1) AU498511B2 (en)
BE (1) BE834939A (en)
CA (1) CA1046509A (en)
CH (2) CH618707A5 (en)
DE (1) DE2548087A1 (en)
DK (1) DK146803C (en)
ES (1) ES442144A1 (en)
FR (1) FR2289203A1 (en)
GB (1) GB1470860A (en)
NL (1) NL7512489A (en)
SE (1) SE423996B (en)
SU (2) SU646913A3 (en)
YU (2) YU37119B (en)
ZA (1) ZA756732B (en)

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1506200A (en) * 1975-04-30 1978-04-05 Farmaceutici Italia Glycosides
GB1502121A (en) * 1975-08-02 1978-02-22 Farmaceutici Italia Anthracyclines
GB1524468A (en) * 1976-07-13 1978-09-13 Farmaceutici Italia Anthracylines
GB1561507A (en) * 1976-11-17 1980-02-20 Farmaceutici Italia Snthracycline disaccharides
GB1573036A (en) * 1977-05-05 1980-08-13 Farmaceutici Italia Anthracyclines
GB1573037A (en) * 1977-05-05 1980-08-13 Farmaceutici Italia Anthracyclines
US4181795A (en) * 1978-05-22 1980-01-01 Purdue Research Foundation Daunosamine synthesis
US4203976A (en) * 1978-08-02 1980-05-20 Merck & Co., Inc. Sugar derivatives of C-076 compounds
US4303785A (en) * 1978-08-05 1981-12-01 Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai Antitumor anthracycline antibiotics
JPS5756494A (en) * 1980-09-22 1982-04-05 Microbial Chem Res Found New anthracyclin derivative
JPS6130464U (en) * 1984-07-26 1986-02-24 武夫 安田 dishwashing utensils
JPH01207028A (en) * 1987-02-09 1989-08-21 Tomiko Saito Scrubbing brush and container
JPH0261920U (en) * 1988-10-28 1990-05-09
JP3035035U (en) * 1996-04-26 1997-03-11 裕敬 丸子 Sponge with handle
DE69842005D1 (en) * 1997-12-05 2010-12-30 Mercian Corp CRYSTALLINE ANTHRACYCLIN ANTIBIOTICUM AND ITS MANUFACTURE

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3803124A (en) * 1968-04-12 1974-04-09 Farmaceutici It Soc Process for the preparation of adriamycin and adriamycinone and adriamycin derivatives
BE793976A (en) * 1972-01-13 1973-05-02 Parke Davis & Co NEW POLYAMINES AND PROCESS FOR PREPARING THEM

Also Published As

Publication number Publication date
GB1470860A (en) 1977-04-21
YU269575A (en) 1983-04-27
SU646913A3 (en) 1979-02-05
SE423996B (en) 1982-06-21
AU8604075A (en) 1977-05-05
AU498511B2 (en) 1979-03-15
JPS59104397A (en) 1984-06-16
BE834939A (en) 1976-04-28
AT340591B (en) 1977-12-27
CH621799A5 (en) 1981-02-27
JPS6056720B2 (en) 1985-12-11
FR2289203A1 (en) 1976-05-28
ZA756732B (en) 1976-10-27
CA1046509A (en) 1979-01-16
DK482175A (en) 1976-04-30
CH618707A5 (en) 1980-08-15
JPS5168561A (en) 1976-06-14
YU293381A (en) 1985-04-30
NL7512489A (en) 1976-05-04
DK146803C (en) 1984-06-18
YU37119B (en) 1984-08-31
ATA812975A (en) 1977-04-15
DK146803B (en) 1984-01-09
FR2289203B1 (en) 1978-11-10
JPS5951559B2 (en) 1984-12-14
ES442144A1 (en) 1977-08-01
SE7512005L (en) 1976-04-30
US4025623A (en) 1977-05-24
DE2548087A1 (en) 1976-05-06

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